About UNTHSC Scholar
Contact scholar@unthsc.edu for more information on how to submit your work.
UNTHSC Scholar is an open access repository of the intellectual output and publicly available materials of the university. UNTHSC Scholar provides stable access to data, highlights community partnerships and engagement, and enables discovery of these works by the international scientific community. It preserves the history, growth and innovation of the University of North Texas Health Science Center as an institution.
Communities in UNTHSC Scholar
Select a community to browse its collections.
Recent Submissions
A Retrospective Analysis of Outcomes with Pulmonary Artery Catheter Use in Patients Diagnosed with Cardiogenic Shock
(2024-08) Hollinger, Tess S.; Bunnell, Bruce A.; Liu, Ran; Felius, Joost
The primary goal of this study is to observe which timing variable of pulmonary artery catheter (PAC) insertion, or no PAC insertion is related to better in-hospital outcomes of patients with cardiogenic shock. Furthermore, additional variables like sex and health history are tested to see if they affect the relationship of PAC timing and inhospital outcomes. Data were retrospectively collected from the CSWG registry at a single center, BUMC. All variables collected were redacted and combined to form a dataset. From here I used the PAC timing and cardiogenic shock diagnosis variables to manually place patients into groups for analysis. The groups used were Prior (PAC placement before cardiogenic shock diagnosis), Early (PAC placement within 6 hours or less of cardiogenic shock diagnosis), Delay (PAC placement after 6 hours of diagnosis), None (no PAC use). 227 patients' data was collected and used for analysis. The only groups that were observed to have a significant difference in in-hospital outcomes were the Prior and Delay groups that have a significant decrease in in-hospital mortality in comparison to the Early group. The results of the analyses support that PAC timing groups Prior and Delay have less in-hospital mortality when compared to the Early group. There were no other findings to draw statistically significant conclusions from.
ADAM19 and ADAMTS4 expression in Human Optic Nerve Head Astrocytes
(2024-05) Easo, Tony; Tovar-Vidales, Tara; Inman, Denise; Rosales, Armando
Summary: Glaucoma is characterized by the degeneration and death of retinal ganglion cells (RGCs) and their axons, causing irreversible blindness. Various risk factors contribute to glaucoma onset, including intraocular pressure (IOP), age, and family history (1). In glaucoma, the primary site of damage is the optic nerve head (ONH), specifically the lamina cribrosa (LC) region. The ONH undergoes significant stress and structural changes in response to elevated IOP, leading to the death of RGCs (2). ONH astrocytes, a major cell type in the LC, are believed to play a significant role in the pathological remodeling of the extracellular matrix (ECM) during glaucoma. These cells respond notably to biomechanical stresses and increased levels of the fibrotic cytokine transforming growth factor beta 2 (TGFβ2), which is commonly found in the aqueous humor, trabecular meshwork, and optic nerve head (ONH) of glaucoma patients (2). Our lab has previously shown that ONH tissues treated with TGFβ2 show an increase in proteins that could be involved in glaucoma pathology. In this study, we primarily investigated the expression and regulation by TGFβ2 of A Disintegrin and Metalloproteinase (ADAM19) and ADAM with thrombospondin motifs (ADAMTS4) in ONH astrocytes. Hypothesis: IOP and remodeling of the ECM in the LC of the ONH are hallmarks of the pathogenesis of glaucoma. TGFβ2 is a profibrotic cytokine known to induce the synthesis and deposition of ECM. TGFβ2 increases ECM synthesis and deposition by ONH astrocytes within the LC, and RNA sequencing showed disintegrin and metalloproteinases (ADAMs) and ADAM with thrombospondin motifs (ADAMTS) were significantly dysregulated with TGFβ2 treatment compared to controls. Our lab has previously demonstrated that human ONH cells derived from glaucoma donors or treated with exogenous TGFβ2 increase profibrotic miRNAs and decrease anti-fibrotic miRNAs. MiR29c specifically, has been predicted to regulate members of the ADAM family proteins. Given that ADAMs and ADAMTS4 influence cell phenotype by modulating the ECM through cell adhesion, migration, proteolysis, and signaling pathways (19), we hypothesize that ONH astrocytes express ADAM19 and ADAMTS4 and that TGFβ2 and miR29c regulates ADAM19 and ADAMTS4 expression in ONH astrocytes. Significance: The existing treatments for glaucoma primarily focus on reducing IOP, which has proven effective in slowing the progression of the condition in many cases; however, it falls short of halting vision loss. To fully comprehend the intricacies of glaucoma pathology, investigating the expression of ADAM proteins in response to treatment with or without TGFβ2 in ONH astrocytes can provide insights that contribute to a better understanding of the disease and, potentially, the development of more holistic therapeutic approaches.
The Functional Role of Lectin-like Transcript 1 (LLT1) in Hepatocellular Carcinoma
(2023-08) Perkins, Joshua; Mathew, Stephen O.; Sankpal, Umesh; Basha, Riyaz; Chaudhary, Pankaj; Jones, Harlan P.
Hepatocellular carcinoma (HCC) is a global leading cause of cancer-related deaths. Current treatments for HCC are ineffective. Transplantation and surgical resection are the only curative options, however, only an approximate 3% of HCC patients are eligible. Without transplantation or resection, the 5-year, overall survival (OS) rates remain <10%, with death 6-18 months from diagnosis. Cancer immunotherapy provides an avenue to investigate potential treatments as immunotherapies can promote immune-mediated tumor lysis, while sparing patients from some of the toxic effects of radiation and chemotherapy. Prior research suggests the inhibitory mechanisms underlying the LLT1/NKR-P1A interaction attributes to cancer growth as it allows the cancer to evade immune surveillance. Studies demonstrate improved NK cell activity and NK cell-mediated tumor lysis upon applying LLT1 blockades in prostate, breast, and hematological cancers. The goal of this project was to similarly evaluate the role of LLT1 in HCC.
MECHANISM OF ACTION AND DRUG DELIVERY OF HYBRID NITRIC OXIDE DONATING AND ANTIOXIDANT SMALL MOLECULES IN EXPERIMENTAL MODEL OF OCULAR HYPERTENSION
(2024-05) Amankwa, Charles E.; Acharya, Suchismita; Krishnamoorthy, Raghu R.; Stankowska, Dorota L.; Karamichos, Dimitrios; Ellis, Dorette Z.; Mathis, Michael
Primary open angle glaucoma (POAG) belongs to a group of optic neuropathies characterized by the damage to the optic nerve head, and the slow progressive deterioration of retinal ganglion cells (RGCs). POAG is predominantly asymptomatic in its early phases, and the leading cause of irreversible blindness globally. The underlying mechanisms of POAG include but not limited to; elevated intraocular pressure (IOP), excitotoxicity, and oxidative stress. Additionally, reduced trabecular meshwork (TM) cellularity, viability and decreases in antioxidant enzymes have been reported to be implicated in the pathogenesis of POAG. Currently, IOP reduction remains the mainstay for slowing down the progression of RGC degeneration and TM cell death. However, IOP lowering alone does not eliminate the progressive neurodegeneration events. Therefore, the development of novel therapeutic strategies that can reduce IOP and simultaneously provide neuroprotective benefits is essential for the effective management of POAG. To this end, we designed and synthesized novel hybrid nitric oxide donor and antioxidant small molecules (SA-2, SA-9, and SA-10) with the goal of lowering IOP and providing neuroprotection in experimental models of glaucoma. In the present study, we evaluated the in-vitro efficacy of SA-analogs in protecting TM cells from oxidative stress induced cell death. Additionally, we aimed at understanding the mechanism of action of SA-2 and assessed its in-vivo IOP lowering efficacy and toxicity profile in PLGA encapsulated nanoparticles after topical administration. Considering that less than 5% of a topically applied drug reaches intraocular tissues due to limited ocular absorption, rapid precorneal drug elimination, and the corneal epithelial barrier, our overarching goal was to provide a sustained and prolonged IOP lowering effect to reduce the frequency of dosing and potential adverse effects to ocular tissues. We demonstrated the utility of SA-2, SA-9, and SA-10 as novel strategies to promote survival of TM cells by scavenging reactive oxygen species. We found that SA-2 and the second-generation sulfur containing hybrid NO donor-antioxidants: SA-9 and its active metabolite SA-10 scavenged broad-spectrum ROS while maintaining NO bioavailability. We observed significant improvement in antioxidant enzymes following treatment with SA-2. Notably, catalase, glutathione peroxidase and total antioxidant enzyme levels were increased with SA-2 treatment along with increased TM mitochondrial respiration. Our studies showed that the SA-2 encapsulated in PLGA polymer was readily bioavailable to both the anterior segment and posterior regions of the eye. This observation reflected in the sustained IOP reduction of SA-2 lasting for 6 days with no overt toxicity and functional decline in C57BL6/J mice eyes. In summary, this dissertation project provides an alternate therapeutic strategy in the management of POAG. Our modified formulation of SA-2NPs is a promising candidate for a sustainably reducing IOP while providing neuroprotection to the RGCs and TM.
Evaluating the Association of Gender as it Pertains to Health-Related Quality of Life Outcomes in Chronic Low Back Pain Patients
(2024-05) Slater, Madeline L.; Cunningham, Mark W., Jr.
BACKGROUND: Six hundred and nineteen million individuals worldwide are affected by low back pain, with this number estimated to increase to 850 million by the year 20501. Low back pain is also the leading cause of disability worldwide2 and contributes to the limitation of activities and needing leave from work resulting in severe medical burdens and economic costs3,4. Males and females (referred to as gender throughout this project based on variables in the NIH Minimum Dataset form for Chronic Low Back Pain) have recorded differences in chronic low back pain outcomes including, but not limited to, treatment outcomes and psychosocial outcomes. Individuals with female sex traditionally take on the female gender with associated norms and roles, and those with male sex often take on male gender and associated roles. Previous literature on this topic varies by location and typically reports on local patients. The PRECISION Pain Research Registry differs from other research projects because the participants involved in this study are from locations within the continental United States. This diversity in terms of location, ethnicity, and race of study participants allows a larger and more applicable representation of the U.S. population in terms of chronic low back pain management. Discrepancies on whether gender has an effect on health-related quality of life outcomes in chronic low back pain patients in the literature is controversial. Thus the link between gender and chronic low back pain outcome is unknown and is the focus of this study, in which we will use the PRECISION Pain Research Registry to examine the relationship. HYPOTHESIS: We hypothesize that males and females with chronic low back pain have different health-related quality of life outcomes and these differences are correlated to pain catastrophizing and pain-self efficacy scores. The specific aims of the project include (1) analyzing the association between gender and pain catastrophizing in chronic low back pain patients, (2) analyzing the association between gender and pain self-efficacy scores in chronic low back pain patients, and (3) using repeated measures to assess differences between males and females in chronic low back pain outcomes pertaining to health-related quality of life over a 12-month period. METHODS: Data from 1,478 patients in the Pain Registry for Epidemiological, Clinical, and Interventional Studies and Innovation (PRECISION) were analyzed using factors such as gender, age, race, ethnicity, smoking habits, low back pain duration, opioid use for low back pain treatment, occurrence of low back pain surgery, education level, comorbidities, non-pharmacological treatments, and body mass index (BMI). Importantly, this project conducted analysis to determine the association between gender and pain catastrophizing, pain self-efficacy, and health-related chronic low back pain outcomes. The health-related quality of life outcomes of sleep disturbance, pain interference, anxiety, depression, and energy levels are taken from the negative outcomes from the Patient-Reported Outcomes Measurement Information System (PROMIS) scale. RESULTS: Overall, there were no statistically significant associations between gender and pain catastrophizing scores with males having slightly higher scores compared to females. No association was seen between gender and pain self-efficacy. Male patients once again had slightly higher scores but the mean score difference was not significant. Results from interaction term analysis showed that pain catastrophizing and pain self-efficacy scores on their own have an effect on SPADE health-related quality of life outcomes but upon the introduction of gender, the effect becomes negligible.